Project Summary Research conducted within the Duke University?s Superfund Research Center (DUSRC) focuses on a central research question: How does early life exposure to hazardous substances elicit developmental toxicity, and what are the later-life consequences? As such the theme of our center is ?Developmental Exposures: Mechanisms, Consequences and Remediation?, and we remain committed to investigating the vulnerability of the developing organism to hazardous chemical exposures. Within the DUSRC we emphasize research on both ATSDR priority chemicals (e.g. PAHs, metals, organophosphate chemicals) and emerging chemicals of concern (e.g. halogenated flame retardants) that are known to, or have potential to, adversely effect development. Mechanisms of action that are central to the mission and research conducted within the DUSRC include mechanisms underlying molecular and physiological effects from developmental exposures, mechanisms underlying ameliorations of and adaptations to these effects, and mechanisms and approaches to engineering solutions for the ultimate removal of these chemicals from the environment. A unifying theme across the DUSRC projects is effects on neurobehavioral and neurodevelopmental outcomes from these exposures. DUSRC researchers are conducting research using in vitro (e.g. cell culture) and in vivo (e.g. zebrafish, rats) models to determine effects of these hazardous chemicals on neurodevelopmental across projects, but several individual projects are also exploring effects on skeletal and fat development, cardiovascular development and bioenergetics. Of key interest is the ability of some contaminants to converge on similar phenotypes through multiple mechanisms of action. With the heightened interest in developing Adverse Outcome Pathways (AOPs) within regulatory agencies, the DUSRC is well poised to support these endeavors. Our interdisciplinary team of biomedical/environmental scientists and engineers provide the DUSRC with a unique opportunity to address and examine ?holistic? consequences of developmental exposures. This integration is central to evaluating the true risk from exposure to hazardous substances. The DUSRC directly addresses the program mandates by investigating health effects and risks and remediation of hazardous substances in an interdisciplinary fashion. In addition to responding to SRP mandates, the DUSRC?s research, research translation, and community engagement activities are also highly relevant to numerous stakeholders, including the Environmental Protection Agency.